Aug 2026· Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie· Vol 203, pp.
119888
· 0 citations· 346 references
Medicine
TL;DR
A structured translational roadmap is proposed that prioritizes biologically predictive design, fit-for-purpose safety assessment, scalable good manufacturing practice production, early regulatory alignment, and clinically meaningful benefit over unnecessary structural complexity.
Abstract
Nanomaterial-based drug delivery systems (NDDS) have become enabling technologies for small-molecule reformulation, RNA medicines, vaccines, gene editing, immunotherapy, and regenerative therapeutics. Their clinical performance, however, is determined not only by cargo loading and release but also by protein-corona evolution, immune recognition, biological-barrier navigation, intracellular trafficking, manufacturing control, and regulatory fit. This review provides a cross-platform comparison of lipid nanoparticles, polymeric nanoparticles, inorganic nanomaterials, extracellular vesicles (EVs), and biomimetic nanocarriers with respect to cargo compatibility, targeting potential, circulation behavior, scalability, clinical maturity, and regulatory status. Passive, active, biomimetic, and organ-selective targeting strategies are critically compared, and recent advances in extrahepatic lipid nanoparticle delivery, biodegradable ionizable lipids, programmable polymers, EV manufacturing, and nano-bio interactions are evaluated. We further integrate disease applications with quantitative lessons from approved products and representative clinical attrition, and compare regulatory expectations across major US, European, Japanese, Chinese, and ICH frameworks. Emerging computational approaches-including high-throughput screening, machine-learning-guided material discovery, autonomous formulation laboratories, generative design, and digital twins-are discussed alongside their validation requirements. A structured translational roadmap is proposed that prioritizes biologically predictive design, fit-for-purpose safety assessment, scalable good manufacturing practice production, early regulatory alignment, and clinically meaningful benefit over unnecessary structural complexity.
Exosome-based drug delivery systems have emerged as a promising platform for targeted therapeuticsand precision medicine because of their excellent biocompatibility, low immunogenicity, and intrinsicability to transport diverse therapeutic molecules. Unlike conventional nanocarriers, exosomesefficiently deliver proteins, nucleic acids, and small-molecule drugs while overcoming biologicalbarriers, including the blood–brain barrier. This review highlights the biological characteristics,biogenesis, sources, isolation, purification, and characterization techniques of exosomes. It alsodiscusses recent advances in drug-loading strategies, surface engineering, and exosome modification toimprove targeting efficiency and therapeutic performance. Furthermore, the review summarizes theapplications of exosome-based drug delivery in cancer, neurological disorders, cardiovascular diseases,inflammatory conditions, infectious diseases, regenerative medicine, and gene therapy. Despite theirremarkable therapeutic potential, challenges related to large-scale production, standardization, storagestability, and regulatory approval remain significant barriers to clinical translation. Continued researchand technological advancements are expected to facilitate the successful integration of exosome-basedtherapeutics into personalized healthcare.
Snehal Dasharath Pawar, Anis Fathima M S, Nikitha A C et al.· The Bioscan· 0 citations
RNA therapeutics have emerged as versatile platforms for gene modulation and protein expression in vaccination, oncology, genetic disorders, and inflammatory diseases. However, their broader clinical application remains limited by inefficient delivery, insufficient tissue specificity, inadequate intracellular bioavailability, and long-term safety concerns. This review examines non-viral and non-lipid RNA nanocarriers from mechanistic and translational perspectives. We outline the cargo-specific delivery requirements of various RNA modalities and analyze polymeric nanoparticles, inorganic nanomaterials, peptide- and protein-based carriers, and virus-like particles as distinct strategies to overcome extracellular, tissue-level, cellular, and intracellular barriers. Cross-platform trade-offs are evaluated based on RNA association and release, cargo compatibility, administration route, biodegradability, immune interactions, and manufacturability. We further discuss how carrier architecture influences biodistribution, intracellular RNA activity, and therapeutic efficacy across major disease areas. Clinically validated lipid nanoparticle (LNP) formulations serve as translational benchmarks, while non-lipid systems are evaluated based on productive delivery, release efficiency, repeat-dose compatibility, long-term material fate, scalability, and regulatory feasibility. By integrating cargo requirements, barrier resolution, intracellular trafficking, and translational benchmarking, this review highlights non-viral and non-lipid nanocarriers as complementary platforms for context-specific RNA therapy.
Mingxia Jiang, Qiannan Cao, Huapan Fang et al.· Journal of Controlled Releas...· 0 citations
RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines.
Mohannad M. Fallatah, Samiyah Al-Khaldi, Dimah K. Alrabiah et al.· Pharmaceutics· 0 citations
INTRODUCTION
Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems.
AREAS COVERED
This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release.
EXPERT OPINION/COMMENTARY
Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.
Nithya Ajay, Anu Shibi Anilkumar, R. Veerabathiran· Therapeutic delivery· 0 citations
Peptide-based therapeutics have become a flexible type of medicine that combines high target specificity and strong biological activity with good safety profiles. They effectively connect small-molecule drugs and biologics. Since insulin was first used in 1922, more than 100 peptide drugs have been approved around the world, and their use is growing in diabetes, cancer, rare diseases, and autoimmune disorders. However, their clinical use is still limited by rapid enzymatic degradation, short half-life, poor membrane permeability, low oral bioavailability, and formulation instability. This review presents a unified innovation framework that integrates upstream molecular engineering strategies including cyclization, peptide stapling, D- and β-amino acid substitution, PEGylation, and backbone modification with downstream advanced delivery platforms such as nanocarriers, microneedles, self-assembling hydrogels, and stimuli-responsive systems, while also addressing critical translational considerations including scalability, regulatory requirements, and manufacturing consistency. By critically linking structural modifications at the molecular level with formulation performance and clinical translation factors, and by evaluating both approved products and persistent gaps in predictive modelling and patient-centric delivery, this work offers practical insights that go beyond the scope of most existing reviews. The integrated perspective presented here highlights how these combined approaches are shifting peptide therapeutics from conventional injectable formats toward more stable, convenient, and precisely targeted solutions, paving the way for the next generation of patient-friendly peptide medicines.
Pradip Karale, Saloni Borse, Anjali Gavit et al.· Journal of Pharmaceutical In...· 0 citations
Peptides and proteins have become central to modern therapeutics because of their high biological specificity and ability to modulate targets that are often inaccessible to small molecules. However, their clinical use remains constrained by molecular instability, enzymatic degradation, rapid systemic clearance, poor epithelial permeability, immunogenicity risk, and the practical burden of repeated parenteral administration. Polymeric delivery systems offer versatile strategies to address these limitations through molecular conjugation, biodegradable depots, nanoparticles, micelles, hydrogels, nanogels, mucoadhesive systems, and microneedle-based platforms. This review summarizes the design principles, biological barriers, formulation challenges, and translational considerations that govern polymeric peptide and protein delivery. Particular emphasis is placed on polymer-cargo interactions, stability preservation, controlled release versus polymer degradation, critical quality attributes, safety, immunogenicity, manufacturability, and regulatory complexity. Clinically mature examples, including PEGylated proteins and PLGA/PLA-based long-acting depots, demonstrate that polymeric technologies can improve pharmacokinetics and dosing convenience when the delivery objective is clearly defined and product complexity remains manageable. In contrast, many nanoscale, mucosal, and stimuli-responsive systems remain limited by weak in vitro-in vivo translation, incomplete characterization of released cargo bioactivity, scale-up difficulty, and uncertain regulatory pathways. Future progress will require development strategies that begin with clinical need and target product profile rather than platform novelty alone. Successful polymeric systems are likely to be those that integrate protein stability, controlled exposure, patient usability, robust manufacturing, validated analytics, and regulatory clarity into a coherent product-development framework.
Ayman M. Al-Qaaneh, Mai S Khanfar· International journal of pha...· 1 citation
